Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.9.3.1 (
cytochrome oxidase
)
8,822
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Studies in animal models of myocardial ischemia-reperfusion revealed that the administration of insulin-like growth factor (
IGF-1
) can provide substantial cardioprotective effect. However, the mechanisms by which
IGF-1
prevents myocardial ischemia-reperfusion injury are not fully understood. This study addresses whether mitochondrial bioenergetic pathways are involved in the cardioprotective effects of
IGF-1
. Single cardiomyocytes from adult rats were incubated in the absence or presence of
IGF-1
for 60 min and subjected to 60 min hypoxia followed by 30 min reoxygenation at 37 degrees C. Mitochondrial function was evaluated by assessment of enzyme activities of oxidative phosphorylation and Krebs cycle pathways. Hypoxia/reoxygenation (HR) caused significant inhibition of mitochondrial respiratory
complex IV
and V activities and of the Krebs cycle enzyme citrate synthase, whereas pretreatment with
IGF-1
maintained enzyme activities in myocytes at or near control levels. Mitochondrial membrane potential, evaluated with JC-1 staining, was significantly higher in
IGF-1
+ HR- treated myocytes than in HR alone, with levels similar to those found in normal control cardiomyocytes. In addition,
IGF-1
reduced both HR-induced lactate dehydrogenase (LDH) release and malondialdehyde production (an indicator of lipid peroxidation) in cardiomyocytes. These results suggest that
IGF-1
protects cardiomyocytes from HR injury via stabilizing mitochondria and reducing reactive oxidative species (ROS) damage.
...
PMID:Mitochondrial involvement in IGF-1 induced protection of cardiomyocytes against hypoxia/reoxygenation injury. 1726 81
Oxidative stress and mitochondrial dysfunction have been described in Huntington's disease, a disorder caused by expression of mutant huntingtin (mHtt).
IGF-1
was previously shown to protect HD cells, whereas insulin prevented neuronal oxidative stress. In this work we analyzed the role of insulin and
IGF-1
in striatal cells derived from HD knock-in mice on mitochondrial production of reactive oxygen species (ROS) and related antioxidant and signaling pathways influencing mitochondrial function. Insulin and
IGF-1
decreased mitochondrial ROS induced by mHtt and normalized mitochondrial SOD activity, without affecting intracellular glutathione levels.
IGF-1
and insulin promoted Akt phosphorylation without changing the nuclear levels of phosphorylated Nrf2 or Nrf2/ARE activity. Insulin and
IGF-1
treatment also decreased mitochondrial Drp1 phosphorylation, suggesting reduced mitochondrial fragmentation, and ameliorated mitochondrial function in HD cells in a PI-3K/Akt-dependent manner. This was accompanied by increased total and phosphorylated Akt, Tfam, and mitochondrial-encoded cytochrome c oxidase II, as well as Tom20 and Tom40 in mitochondria of insulin- and
IGF-1
-treated mutant striatal cells. Concomitantly, insulin/
IGF-1
-treated mutant cells showed reduced apoptotic features. Hence, insulin and
IGF-1
improve mitochondrial function and reduce mitochondrial ROS caused by mHtt by activating the PI-3K/Akt signaling pathway, in a process independent of Nrf2 transcriptional activity, but involving enhanced mitochondrial levels of Akt and mitochondrial-encoded
complex IV
subunit.
...
PMID:Insulin and IGF-1 improve mitochondrial function in a PI-3K/Akt-dependent manner and reduce mitochondrial generation of reactive oxygen species in Huntington's disease knock-in striatal cells. 2499 36
